Beta-blockers


Family of drugs widely used to treat arterial hypertension and angina, as well as for local treatment of glaucoma.
 
Three problems:
  • Beta-blockers and asthma
     
  • Beta-blockers and anaphylactic shock
     
  • Beta-blockers and local allergic effect
Incidence
One 40 or 80 mg tablet of propranolol can induce bronchoconstriction in 50% of asthmatics, but the rate is probably much lower with cardioselective beta-blockers.
 
Bronchoconstriction also occasionally occurs in patients with chronic bronchitis. 13 deaths and 200 major reactions to timolol maleate eye drops have been reported in asthmatics in the USA.
 
Beta-blockers and anaphylactic shock: unknown.
 
Beta-blockers in eye-drops are widely used for the treatment of glaucoma; the local allergic effect has recently been recognized.
 
Clinical manifestations
Asthma, bronchospasm, dyspnea, apnea in children, respiratory arrest.
 
Anaphylactic shock to beta-blockers is characterized by bradycardia, despite collapse and poor response to epinephrine.
 
Eczema of the eyelids, contact conjunctivitis with beta-blockers containing eye-drops.
 
Diagnostic methods
Beta-blockers and asthma: clinical signs and spirometric data.
 
Beta-blockers and anaphylactic shock: clinical signs.
 
Beta-blockers and eczema: patch-tests 0.5% aq. or pure eye-drops.
 
Mechanisms
The mechanism underlying the ability of beta-blockers to produce bronchoconstriction remains unclear.
 
Beta-blockers and anaphylactic shock: beta-blockers inhibits the production of cyclic AMP (by reducing intracellular levels) and lower the threshold of mediator release by mastocytes and basophils. Beta-blockers decrease endogenous adrenaline secretion by blocking beta-2-receptors at synapses, and inhibit beta 1 effects of exogenous and endogenous adrenaline on the heart.
 
In contact allergy, beta-blockers have a very close structure; most of them cross-react. This may be due to a common aldehyde after primary metabolism.
 
Management
Beta-blockers and asthma:
 
- If a beta-blocker must be administered to an asthmatic pa tient, use a selective beta 1 agent, if necessary determined by quantitative measurement of cardioselectivity:
 
Clinical surveillance and spirometry at the time of administration.
 
Administration in hospital:
 
Day 1:   1/10th of the dose.
Day 2:   1/5th of the dose.
Day 3:   1/2 of the dose.
Day 4:   full dose.

- If beta-blocker eye drops must be administered to an asthmatic patient, first test tolerance, e.g. to timolol: instillation of one drop of timolol collyre at 0.50% in each eye followed by second instillation 20 minutes later; clinical surveillance (chest auscultation, pulse and arterial blood pressure) at start then at 15, 30, 60 and 120 minutes; perform spirometry at the same time.
 
- The best agent available at the present time is a beta 1 selective product: betaxolol.
 
Beta-blockers and anaphylactic shock:
 
Curative treatment:
  • refractory to adrenaline;
     
  • use of isoprenaline, dopamine, or glucagon;
     
  • need for blood volume expansion (6 to 7 l).
Preventive treatment:
  • Skin-test and desensitization under beta-blockers is prohibited.
     
  • For anesthesia, either discontinue beta-blockers 48 hours before surgery, or perform an isoprenalin test during surgery (seldom done).
Beta-blockers and contact eczema with eye-drops:

Avoidance. The risk of recurrence is high if another local beta-blocker is used.

References

  1. Giordano-Labadie F, Lepoittevin J.P, Calix I, Bazeix J, "Allergie de contact aux bloqueurs des collyres: allergie croisée ?", Ann. Dermatol. Venereol., 1997; 124: 322-4
  2. Tattersfield A.E, "Beta adrenoreceptor antagonists and respiratory disease", J. Cardiovasc. Pharmacol., 1986; 8 (S 4), 35-9.
  3. Dunn T.L, Gerber M.J, Shen A.S, Fernandez E, Iseman M.D, Cherniack R.M, "The effect of topical ophthalmic instillation of timolol and betaxolol on lung function in asthmatic subjects", Am. Rev. Respir. Dis., 1986; 133:
    264-8.
  4. Benitah E, Nataf P, Herman D, "Accidents anaphylactiques chez des patients traités par bêtabloquants. A propos de 14 observations", Thérapie, 1986; 41: 139-42.

As in all diagnostic testing, the diagnosis is made by the physican based on both test results and the patient history.